title: Frataxin participates to the hypoxia-induced response in tumors.
abstract: Defective expression of frataxin is responsible for the degenerative disease Friedreich's ataxia. Frataxin is a protein required for cell survival since complete knockout is lethal. Frataxin protects tumor cells against oxidative stress and apoptosis but also acts as a tumor suppressor. The molecular bases of this apparent paradox are missing. We therefore sought to investigate the pathways through which frataxin enhances stress resistance in tumor cells. We found that frataxin expression is upregulated in several tumor cell lines in response to hypoxic stress, a condition often associated with tumor progression. Moreover, frataxin upregulation in response to hypoxia is dependent on hypoxia-inducible factors expression and modulates the activation of the tumor-suppressor p53. Importantly, we show for the first time that frataxin is in fact increased in human tumors in vivo. These results show that frataxin participates to the hypoxia-induced stress response in tumors, thus implying that modulation of its expression could have a critical role in tumor cell survival and/or progression.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, Laboratory of Signal Transduction, University Tor Vergata, Rome, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Guccini
authors.forename: D
authors.initials: D
authors.lastname: Serio
authors.forename: I
authors.initials: I
authors.lastname: Condò
authors.forename: A
authors.initials: A
authors.lastname: Rufini
authors.forename: B
authors.initials: B
authors.lastname: Tomassini
authors.forename: A
authors.initials: A
authors.lastname: Mangiola
authors.forename: G
authors.initials: G
authors.lastname: Maira
authors.forename: C
authors.initials: C
authors.lastname: Anile
authors.forename: D
authors.initials: D
authors.lastname: Fina
authors.forename: F
authors.initials: F
authors.lastname: Pallone
authors.forename: M P
authors.initials: MP
authors.lastname: Mongiardi
authors.forename: A
authors.initials: A
authors.lastname: Levi
authors.forename: N
authors.initials: N
authors.lastname: Ventura
authors.forename: R
authors.initials: R
authors.lastname: Testi
authors.forename: F
authors.initials: F
authors.lastname: Malisan
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000096923:Frataxin
chemical_list: D033862:Iron-Binding Proteins; D016159:Tumor Suppressor Protein p53; D000096923:Frataxin